Boc-Asp(OtBu)-N(Bu)Gly-OEt | 156645-55-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Boc-Asp(OtBu)-N(Bu)Gly-OEt
• 英文别名: tert-butyl (3S)-4-[butyl-(2-ethoxy-2-oxoethyl)amino]-3-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxobutanoate
• CAS: 156645-55-5
• 化学式: C₂₁H₃₈N₂O₇
• 分子量: 430.542
• InChiKey: RWZATVDNJRZJQQ-HNNXBMFYSA-N

物化性质

• 沸点：
  536.4±50.0 °C(predicted)
• 密度：
  1.078±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  15
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Boc-Asp(OtBu)-N(Bu)Gly-OEt 在 N-乙基吗啉 、 盐酸 、 碳酸氢钠 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 13.0h， 生成 {Butyl-[(S)-3-[((S)-1-carbamimidoyl-piperidin-3-ylmethyl)-carbamoyl]-2-(naphthalene-2-sulfonylamino)-propionyl]-amino}-acetic acid ethyl ester; hydrochloride
  参考文献：
  名称：

  Design and Synthesis of Potent and Highly Selective Thrombin Inhibitors

  摘要：

  Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoiminomethyl)piperidine (amidinopiperidine) as a weak, but intrinsically selective, thrombin inhibitor. Elaboration of this molecule provided compounds which inhibit thrombin with K-i's in the range of 20-50 nM and with selectivities of 1000-4000 against trypsin. These inhibitor compounds show a new and unexpected, binding mode to thrombin. Modification of the central building block and then of one of the hydrophobic substituents led to the discovery of a new family of thrombin inhibitors which has reverted td the former binding mode to thrombin. This last class of compounds shows inhibitory activities in the picomolar range; low toxicity; and a short plasma half life which favors its use for an intravenous application. From this series of thrombin;inhibitors, 19f (Ro 46-6240) was selected for clinical development as an antithrombotic agent for intravenous administration.

  DOI：

  10.1021/jm00049a008
• 作为产物：
  描述：

  乙基N-丁基甘氨酸酯 、 叔丁氧羰基-L-天冬氨酸-4-叔丁酯 在 N-乙基吗啉 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 Boc-Asp(OtBu)-N(Bu)Gly-OEt
  参考文献：
  名称：

  Design and Synthesis of Potent and Highly Selective Thrombin Inhibitors

  摘要：

  Thrombin, a serine protease, plays a central role in the initiation and propagation of thrombotic events. An extensive search for new thrombin inhibitors was performed, using an unconventional approach. Screening of small basic molecules for binding in the recognition pocket of thrombin led to the discovery of (aminoiminomethyl)piperidine (amidinopiperidine) as a weak, but intrinsically selective, thrombin inhibitor. Elaboration of this molecule provided compounds which inhibit thrombin with K-i's in the range of 20-50 nM and with selectivities of 1000-4000 against trypsin. These inhibitor compounds show a new and unexpected, binding mode to thrombin. Modification of the central building block and then of one of the hydrophobic substituents led to the discovery of a new family of thrombin inhibitors which has reverted td the former binding mode to thrombin. This last class of compounds shows inhibitory activities in the picomolar range; low toxicity; and a short plasma half life which favors its use for an intravenous application. From this series of thrombin;inhibitors, 19f (Ro 46-6240) was selected for clinical development as an antithrombotic agent for intravenous administration.

  DOI：

  10.1021/jm00049a008